Hif-1α regulates differentiation of limb bud mesenchyme and joint development

作者: Sylvain Provot , Dawn Zinyk , Yasemin Gunes , Richa Kathri , Quynh Le

DOI: 10.1083/JCB.200612023

关键词: Internal medicineCell biologyLimb budEndocrinologyZone of polarizing activityMesenchymeEndochondral ossificationMesenchymal stem cellMesodermBiologyChondrogenesisConditional gene knockout

摘要: Recent evidence suggests that low oxygen tension (hypoxia) may control fetal development and differentiation. A crucial mediator of the adaptive response cells to hypoxia is transcription factor Hif-1α. In this study, we provide mesenchymal condensations give origin endochondral bones are hypoxic during development, demonstrate Hif-1α expressed transcriptionally active in limb bud mesenchyme condensations. To investigate role early chondrogenesis, conditionally inactivated using a Prx1 promoter-driven Cre transgenic mouse. Conditional knockout does not impair condensation, but alters formation cartilaginous primordia. Late hypertrophic differentiation also affected as result delay chondrogenesis. addition, mutant mice show striking impairment joint development. Our study demonstrates crucial, previously unrecognized, chondrogenesis formation.

参考文章(63)
David M. Kingsley, Genetic Control of Bone and Joint Formation The Molecular Basis of Skeletogenesis. ,vol. 232, pp. 213- 234 ,(2001) , 10.1002/0470846658.CH15
Weimin Bi, Jian Min Deng, Zhaoping Zhang, Richard R. Behringer, Benoit de Crombrugghe, Sox9 is required for cartilage formation. Nature Genetics. ,vol. 22, pp. 85- 89 ,(1999) , 10.1038/8792
Hans-Peter Gerber, Thiennu H Vu, Anne M Ryan, Joe Kowalski, Zena Werb, Napoleone Ferrara, None, VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation Nature Medicine. ,vol. 5, pp. 623- 628 ,(1999) , 10.1038/9467
Neil H. Shubin, Pere Alberch, A morphogenetic approach to the origin and basic organization of the tetrapod limb Evolutionary Biology-new York. ,vol. 20, pp. 319- 387 ,(1986) , 10.1007/978-1-4615-6983-1_6
Malcolm Logan, James F. Martin, Andras Nagy, Corrinne Lobe, Eric N. Olson, Clifford J. Tabin, Expression of Cre Recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis. ,vol. 33, pp. 77- 80 ,(2002) , 10.1002/GENE.10092
Lori E. Kotch, Narayan V. Iyer, Erik Laughner, Gregg L. Semenza, Defective Vascularization of HIF-1α-Null Embryos Is Not Associated with VEGF Deficiency but with Mesenchymal Cell Death Developmental Biology. ,vol. 209, pp. 254- 267 ,(1999) , 10.1006/DBIO.1999.9253
Elaine E. Storm, David M. Kingsley, GDF5 Coordinates Bone and Joint Formation during Digit Development Developmental Biology. ,vol. 209, pp. 11- 27 ,(1999) , 10.1006/DBIO.1999.9241
Uwe Kornak, Stefan Mundlos, Genetic disorders of the skeleton: a developmental approach. American Journal of Human Genetics. ,vol. 73, pp. 447- 474 ,(2003) , 10.1086/377110
Stephen H Settle, Ryan B Rountree, Abhishek Sinha, Abigail Thacker, Kay Higgins, David M Kingsley, Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes Developmental Biology. ,vol. 254, pp. 116- 130 ,(2003) , 10.1016/S0012-1606(02)00022-2